Long-term real-world evidence for sustained clinical benefits of fingolimod following switch from natalizumab

Abstract Background The risk of progressive multifocal leukoencephalopathy limits the duration over which patients can receive natalizumab before requiring a switch to other therapies such as fingolimod. To date, no studies have assessed the long-term real-world effectiveness and safety of fingolimod following a switch from natalizumab. We aimed to investigate the benefit–risk profile of fingolimod over 48 months in patients switching from natalizumab, and the impact of washout duration after natalizumab discontinuation on outcomes during fingolimod treatment. Methods This analysis used data from PANGAEA, an ongoing German multicenter, prospective, non-interventional, observational study. In total, 3912 patients were included: 530 had switched from natalizumab (natalizumab subpopulation), and a reference population of 3382 had switched from other treatments or were treatment-naive (non-natalizumab subpopulation). The natalizumab subpopulation was stratified by washout duration (30–89 days, 90–149 days, and ≥ 150 days) prior to fingolimod initiation. Results In the natalizumab subpopulation over 48 months of fingolimod treatment, 58.2% (n = 227/390) of patients remained on fingolimod. Over this period, mean annualized relapse rates (ARRs) and proportions of patients who relapsed were similar across washout durations, and ranged from 0.455 (95% confidence interval [CI]: 0.363–0.571) to 0.546 (95% CI: 0.446–0.669) and 54.1% (n = 92/170) to 60.2% (n = 127/211), respectively. Overall, 17.1% (n = 36/211) had 6-month confirmed disability worsening. In the non-natalizumab subpopulation, ARR was 0.300, 40.9% (n = 1325/3237) of patients relapsed, and a similar proportion to the natalizumab subpopulation had 6-month disability worsening (16.6% [n = 232/1394]). In both subpopulations, the safety profile of fingolimod was consistent with that observed in randomized controlled trials. Conclusions In patients discontinuing natalizumab, fingolimod has a favorable benefit–risk profile over 48 months. These findings also suggest using a short washout following natalizumab discontinuation, consistent with guidelines and current clinical practice in Germany.